Introduction

Sedation of dogs and cats in veterinary practice is daily routine for a variety of procedures, such as radiographs and ultrasonography or other nonpainful, but potentially stressful, procedures. However, historically for avian patients, either manual restraint of conscious birds or general anesthesia is typically performed to complete most clinical procedures. General anesthesia predisposes birds to cardiovascular and respiratory depression and may cause aspiration of gastric or crop contents and hypothermia. In contrast, manual restraint in conscious birds is simple to perform but can have negative consequences, including stress to the bird and/or handler, negative conditioning to the clinic environment (e.g., the person restraining or the towel used for restraint), hyperthermia, and the predisposition of trauma to the handler and/or bird. Several recent studies demonstrated that manual restraint of birds causes increased body temperature and respiratory rate.^1,2 In sick, old, or very stressed birds, acute collapse and death secondary to manual restraint have been reported. Therefore, sedation techniques provide a useful alternative for reducing physiologic stress in birds undergoing nonpainful clinical procedures. Further, sedation in birds provides easier restraint and increases the safety of many clinical procedures (e.g., blood collection, radiography, ultrasonography) and allows for a more complete examination, which would otherwise only be achieved under general anesthesia. Using safe and effective sedative protocols in pet birds provides substantial benefits to the patients as well as the veterinarian and staff, and should be considered for a variety of clinical procedures.

Route of Drug Administration

Historically, sedative drugs have been most commonly administered by intramuscular injection in birds. Intranasal administration of sedative drugs in birds has gained increased attention, and most sedation studies performed in psittacines have used the intranasal route for drug administration. Intranasal administration of midazolam in Hispaniolan Amazon parrots, ring-necked parakeets, budgerigars, and canary finches resulted in rapid onset of dose-dependent degree sedation, which is completely reversible with intranasal flumazenil.^2-5 Intranasal drug administration offers an alternative, noninvasive technique for drug administration in birds (Table 1). It is characterized by its ease of administration, high bioavailability, rapid onset of action, and reduced pain compared to intramuscular administration. Elevation of muscle enzymes in biochemistry panels secondary to intramuscular drug administration is avoided if intranasal administration is used instead. In addition, clients perceive the intranasal route as noninvasive compared to intramuscular injection, which leads to better client compliance in cases in which sedation is recommended. The time to onset of sedation is rapid, typically within 3–5 minutes.^2-5 However, limitations of intranasal administration include incomplete drug delivery due to sneezing during administration, physiologically narrowed nostrils (e.g., cockatoos), or upper respiratory disease (e.g., blocked or stenotic nostrils). In some cases in larger birds (e.g., macaws), the drug volume can also limit the effectiveness and produce excessive sneezing, therefore leading to incomplete drug delivery. Higher concentrated drugs (e.g., midazolam 50 mg/ml, ZooPharm, Windsor, CO) are available, but intramuscular administration might be more feasible in these cases.

Table 1. Comparison of intramuscular and intranasal drug administration in pet birds

Drugs Used for Sedation

Midazolam

Midazolam is currently the most commonly used drug for sedation of pet birds and has a wide margin of safety. Midazolam has sedative, muscle-relaxing, anxiolytic, amnestic, and appetite-stimulating properties in birds.^2,6,7 The injectable form of midazolam (midazolam hydrochloride, 5 mg/ml; Hospira Inc., Lake Forest, IL) or a more concentrated form (50 mg/ml; ZooPharm, Windsor, CO) can be administered intranasally and intramuscularly without side effects.^2-4 Dosages commonly used in pet birds range from 0.5–3 mg/kg.⁸ At the University of Wisconsin, we routinely use 2 mg/kg of midazolam in pet birds, if administered intranasally and as the sole sedative agent. In smaller birds such as finches or budgerigars, we routinely use 4–6 mg/kg of midazolam if administered alone. Doses should be adjusted accordingly in debilitated patients to avoid adverse effects.

Diazepam

Diazepam is of similar efficacy as midazolam in birds following intranasal administration, but it has a longer onset time and duration of action.^4,5,9 While less commonly used for intranasal administration in birds, diazepam represents a suitable alternative in cases in which midazolam might not be available. The intramuscular administration of diazepam should be avoided due to delayed absorption and muscle irritation.⁵ Dosages commonly used in pet birds range from 0.2–2 mg/kg if used as a sole sedative agent. Dosages as high as 10–15 mg/kg have been administered to finches and budgerigars without significant side effects.^4,5,9

Butorphanol

Butorphanol is currently the most commonly used opioid analgesic in birds. Besides its analgesic effects, butorphanol has sedative effects, which are potentiated by benzodiazepines (i.e., midazolam, diazepam). The combined administration of midazolam and butorphanol is recommended in birds for which midazolam alone provides only an insufficient level of sedation or in birds that require deeper sedation for certain clinical procedures (such as radiographic positioning). Butorphanol can be given in combination with midazolam, drawn into a single syringe, and can be given parenterally as well as intranasally. No side effects of intranasal administration of butorphanol at a dose range of 1–3 mg/kg are seen in psittacine birds.⁸ At the University of Wisconsin, we routinely use butorphanol (1–2 mg/kg) combined with midazolam (2 mg/kg) in pet birds administered intranasally or by intramuscular injection. In cockatiels, intranasal sedation with butorphanol (3 mg/kg) combined with midazolam (3 mg/kg) administered intranasally was found to be safe and effective to induce sedation in this species.¹⁰

Reversal of Sedation

Reversal of sedation in pet birds will depend on the patient and the purpose of sedation. Sedation performed in order to facilitate physical examination and diagnostic sample collection should always be reversed, in order to have the patient return to normal behavior and food intake as soon as possible. It is important not to discharge sedated patients, as owners do not tend to appreciate having a partially sedated bird that might be imbalanced, sleepy, and refusing to eat.

Birds that underwent sedation for e-collar or bandage placement or that were sedated for control of seizures should not be reversed. In these cases, birds should be carefully monitored, and reversal considered if the level of sedation is perceived too deep or the duration of sedation is prolonged and might interfere with physiological behavior, particularly food intake.

Flumazenil

Flumazenil is a benzodiazepine antagonist and is used to reverse the sedative effects of midazolam and diazepam in birds.^2,3,8,9 The injectable form of flumazenil (flumazenil hydrochloride, 0.1 mg/ml; Abaxis Pharmaceutical Products, Schaumburg, IL) can be administered intranasally, intramuscularly, or intravenously without side effects. The recommended dosages range from 0.01–0.1 mg/kg. Alternatively, a flumazenil to midazolam ratio of 13:1 has been recommended, but it has been shown that lower doses of flumazenil achieve complete recovery from midazolam-induced sedation in birds.² The author prefers to administer 0.05 mg/kg initially. If reversal is deemed unsatisfactory, then the same amount of flumazenil can be administered repeatedly. Recovery from sedation is usually complete within 10–15 minutes. Reversal with flumazenil is recommended in all birds that are intended to be discharged from the hospital soon after, to avoid injuries from falling off perches and to avoid negative client perception of having a behaviorally abnormal-acting bird. Therefore, it is important to ensure that complete reversal has occurred prior to discharge from the hospital, by assessing complete recovery of the sensory and motor function (e.g., approaching the bird, rotating finger/perch). However, because the half-life of flumazenil is shorter than that of midazolam, re-sedation can occur, and this should be communicated with clients prior to discharge.

Step-by-Step Procedure

1.  Educate the bird owner about what to expect in regard to sedation of their bird. Benzodiazepine-based sedation protocols at the published dosages are safe in healthy pet birds, but birds will appear sleepy, which owners are not used to. Inform them that in some cases regurgitation might occur, particularly in macaws.

2.  Manually restrain the bird using a towel and immobilize the head. Some owners may be able to administer the sedative drugs intranasally, without requiring manual restraint, which will be less stressful to the bird.

3.  Administer the sedative drugs into the nostrils over 5–10 seconds. Split the total dose between both nostrils. If intramuscular administration is performed, administer the sedative drugs by injection in the pectoral muscle using a 25–28-G needle.

4.  Release the bird from manual restraint and allow 7–10 minutes for reaching maximum effect of sedation. Do not allow the bird to perch high; instead, place it on the floor or in its carrier.

5.  Manually restrain the sedated bird. Monitor respiration and heart rate throughout the restraint period. Perform necessary clinical procedures (e.g., physical examination, blood collection, radiographs).

6.  If reversal is indicated, administer flumazenil IM or IN. Split total volume between nostrils. Alternatively, flumazenil can be administered by intramuscular or intravenous injection.

7.  Release the bird on the floor or in its carrier and monitor recovery. Do not allow perching high, so as to avoid trauma from falling, until the bird has completely recovered. Most birds will recover within 10–15 minutes. Assess recovery before discharging the bird. Administer a second dose of flumazenil if recovery is incomplete.

Useful Tips

1.  Each bird requires an individual assessment prior to choosing a suitable sedative drug protocol. Birds that have had no previous experiences with manual restraint may require less sedation than birds that have had previous negative experiences and thereby become readily stressed or fearful in a veterinary clinic environment.

2.  Macaws usually require a combination of midazolam and butorphanol in order to achieve a sufficiently deep level of sedation, suitable for performing a variety of clinical procedures.

3.  Even though a bird might not appear sufficiently deep-sedated while under manual restraint for a clinical procedure, it might become more sedated once stimulation is discontinued, making it unsuitable to be discharged from the hospital. Therefore, every bird that is sedated for a procedure and is intended to be discharged shortly after completion of that procedure, should receive flumazenil. Be aware that re-sedation can occur due to the shorter half-life of flumazenil.

4.  Cockatoos often do not recover completely after the initial dose of flumazenil. A second dose of flumazenil is often necessary. Requiring a second dose of reversal or re-sedation is less common in other species, but it can occur.

Conclusions

Sedation of pet birds offers a practical alternative to manual restraint of conscious birds and to general anesthesia for a large variety of clinical procedures. Sedation decreases the risks of complications by attenuating the side effects of manual restraint and avoids the potentially fatal side effects of general anesthesia (e.g., cardiovascular and respiratory depression, aspiration of crop content). The intranasal route of administration is an alternative noninvasive technique, which has been proven highly effective in birds and usually increases the client compliance on agreeing to sedation for their bird. Intranasal or intramuscular sedation using midazolam, with or without butorphanol, is a simple, safe, effective, reversible, and readily available option for sedation of avian patients in daily clinical practice.

References

1.  Greenacre CB, Lusby AL. Physiologic responses of Amazon parrots (Amazona species) to manual restraint. J Avian Med Surg. 2004;18:19–22.

2.  Mans C, Guzman DSM, Lahner LL, et al. Sedation and physiologic response to manual restraint after intranasal administration of midazolam in Hispaniolan Amazon parrots (Amazona ventralis). J Avian Med Surg. 2012;26:130–139.

3.  Vesal N, Eskandari MH. Sedative effects of midazolam and xylazine with or without ketamine and detomidine alone following intranasal administration in ring-necked parakeets. J Am Vet Med Assoc. 2006;228:383–388.

4.  Sadegh AB. Comparison of intranasal administration of xylazine, diazepam, and midazolam in budgerigars (Melopsittacus undulatus): clinical evaluation. J Zoo Wildl Med. 2013;44:241–244.

5.  Vesal N, Zare P. Clinical evaluation of intranasal benzodiazepines, alpha-agonists and their antagonists in canaries. Vet Anaesth Analg. 2006;33:143–148.

6.  Gilbert DB, Patterson TA, Rose SP. Midazolam induces amnesia in a simple, one-trial, maze-learning task in young chicks. Pharmacol Biochem Behav. 1989;34:439–442.

7.  Farkas L, Crowe SF. The role of the benzodiazepine-GABA system in the memory processes of the day-old chick. Pharmacol Biochem Behav. 2000;65:223–231.

8.  Mans C, Braun J, Feeny M. Intranasal sedation with midazolam or midazolam-butorphanol in psittacine birds: a retrospective evaluation of 114 cases (2010–2012). In: Proc 1st Intl Conf Avian, Herpetol Exot Mammal Med. 2013:292.

9.  Prather JF. Rapid and reliable sedation induced by diazepam and antagonized by flumazenil in zebra finches (Taeniopygia guttata). J Avian Med Surg. 2012;26:76–84.

10.  Doss GA, Fink D, Mans C. Assessment of sedation after intranasal administration of midazolam and midazolam-butorphanol in cockatiels. Am J Vet Res. 2018;79:1246–1252.